Roche Personalised Healthcare

Small differences, big effects

Red 4
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
Red 4 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
There are twelve versions of the brochure, all identical except for the colour of the inside front and back covers.
Our aim is to visualise the core concept of Personalised Healthcare, i.e. the knowledge that some patient subgroups
will benefit particularly well from a medicine due to their genetic makeup. However, the same medication may not
have the desired effect in other patient subgroups (despite the same diagnosis).
Interested? Then read on!
YELLOW1
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
YELLOW 1 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
BLUE1
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
BLUE 1 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
RED1
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
RED 1 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
YELLOW2
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
YELLOW 2 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
BLUE2
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
BLUE 2 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
RED2 RED3
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
RED 2 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
YELLOW3
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
YELLOW 3 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
BLUE3
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
BLUE 3 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
RED4
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
RED 3 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
YELLOW4
Dear reader,
It gives us very great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
YELLOW 4 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
BLUE4
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
BLUE 4 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
of well-defined patient subgroups.
Dear reader,
It gives us great pleasure to present you
with a personalised edition of this brochure.
The copy you are holding is from the
RED 4 group. What does that mean?
We have produced this publication in
twelve different colours. Every reader has
his or her personal copy, and it differs
from over 90 percent of all the other copies.
Not one-hundred-percent individual,
perhaps but still very personal, we hope
youll agree.
And that is precisely what Personalised
Healthcare stands for: These medicines have
not been designed for individual patients
but for use in therapies tailored to the needs
<of well-defined patient subgroups.
Roche Personalised Healthcare 1
 Personalised Healthcare means Our vision of
fitting treatments to different Personalised Healthcare
groups of patients. is becoming reality.

The future of medicine lies

in customisation of this kind.

2 Roche Personalised Healthcare 3


Severin Schwan, CEO Roche
Many heart-to-heart talks with patients and doctors
have brought it home to me just how immense the
need for better or even entirely new diagnoses and
medicines actually is. Our efforts are geared to giving
people with dangerous diseases genuine prospects
for a better and a longer life.
My most important job is to provide our researchers
with an environment that enables them to turn
scientific progress into new, accurately targeted
treatments as effectively as possible.
Personally, I find the advances we have made really
inspiring. They are proof positive that Personalised
Healthcare is the ideal strategy, both for patients and
for Roche itself. Thats what Im here for and the
same goes for our over 80,000 employees.
4 Roche Personalised Healthcare
Personalised Healthcare
The core of our Group strategy
Back in 2006, Roche made Personalised Healthcare central to its Group strategy.
This was the first stage in its commitment to transforming the vision into reality now.
Patients, doctors and payers expect us to deliver new,
safe and effective therapies, making it all the more
important for Roche to systematically pursue its for diagnosis and new medicines for use in the fight
Personalised Healthcare strategy. The economic envi-
ronment is changing constantly and rapidly. It calls
for sturdy, sustainable business models that can keep
pace with changing circumstances. Accordingly, it is
essential for us to
optimise the riskbenefit ratio of therapies
improve the costbenefit ratio of treatments
come up with highly differentiated medicines
bringing clearly defined benefits for patients.
This is why Roche has opted for this approach to the
development of therapies for currently unmet medical
needs, devising the Personalised Healthcare strategy
to cover the demands of the present and the future.
The strategies employed by Roche to respond to these
new challenges are
innovation
drawing upon our core businesses Pharmaceuticals
and Diagnostics to focus exclusively on benefits
for patients.
sight to invest in innovative new approaches like genetic
The aim of Personalised Healthcare is to make modern
medical care more systematic and more effective.
It enables us to identify differences between groups
of patients and improve our understanding of sub-cate-
gories of disease. This knowledge can be used (a) to
find the best targets for new medicines and (b) to come
up with new biomarkers and diagnostic tests.
We want to improve our fundamental understanding
of diseases and their causes. In devising new methods
against diseases, we apply the latest findings of modern
molecular science.
For years now, we have been consistently applying
the Personalised Healthcare strategy at all stages of
development. The rewards are substantial:
many of our new molecular entities have made an
excellent showing in scientific studies
the formal approval of a cancer drug and its compan
ion test in summer 2011 in the USA
the approval of an additional indication of an already
existing cancer drug in the EU.
What does this mean in practical terms?
Our crucial edge comes from interweaving the expertise
of our two Pharmaceuticals and Diagnostics Divisions
and drawing upon it throughout the development
process, all the way up to approval for new diagnostic
tests or new medicines. Very early on, we had the fore-
engineering and related molecular sciences, though
at the time they were still in their infancy. This gave us
a head start.
By combining the specialist knowledge we have in
molecular biology with technology we are able to press
ahead with Personalised Healthcare at an unrivalled
pace. Our unremitting concern is to improve on what
we have achieved so far and to find solutions for the
unanswered medical questions of today.
5
 Standard therapy means Personalised Healthcare means
same syndrome, same therapy. the right therapy for the right group
of patients at the right time.

Patients with same syndrome Group of patients with the same syndrome

One-size-fits-all approach Targeted therapy

6 Roche Personalised Healthcare 7

 Why Personalised Healthcare
is so important
It is more important to know what sort of person has a disease than what sort of
disease a person has. This verdict on the importance of gearing ones healing efforts
to the individual patient rather than the disease was uttered by Hippocrates,
the most famous physician of antiquity.
The modern term for this approach is Personalised
Healthcare. Some 2,400 years after Hippocrates, it is
driving a genuine revolution based on the scientific
realisation that individuals are different and so are
diseases.
Personalised Healthcare aims to provide targeted thera-
pies tailored to the inherited or acquired risk factors
displayed by different subgroups of patients. The foun
dations for this new, highly sensitive approach are the
findings produced by modern research; research that
is able to trace the origins of a disease back to its
molecular causes and thus supply spectacular insights
into the complexity of the factors that lead to disease.
8 Roche Personalised Healthcare
The research work of the last few years has many
Medicines are like suits one size doesnt fit all
important successes to its credit. Today, many patients
are receiving individual diagnoses and targeted thera-
pies. Headlong progress in the sciences related to
molecular biology genetics, genomics, proteomics
is broadening the foundations for progress of this kind,
so it is safe to predict that in the near future many
more patients will benefit from such new approaches.
In its Personalised Healthcare strategy, Roche draws
upon the knowledge supplied by modern molecular
biology in a variety of ways: Out of ten patients treated on average about half of them benefit.
identifying subgroups of patients traditionally For some the treatment wont have any effect, and some may even suffer from side effects.
regarded as having the same disease. This line of
inquiry establishes whether the genetic constitution
of patients cancer displays similar symptoms but
requires different treatments
monitoring the success of a therapy, for example the
results of treatment for hepatitis C or osteoporosis
adjusting the duration of therapy to the individual
needs of a patient, for example in the case of
hepatitis C
administering a medicine (say, a cancer medicine)
Genetics Proteomics
at precisely the right time Genetics is the study of the regularities and the Proteomics is the study of the form, function and
developing products (diagnostic tests and medicines) material foundations involved in the way hereditary interactions of proteins in an organism. Unlike the
systematically and efficiently. features take shape and hereditary systems (genes) relatively static genome, the proteome is a dynamic
are passed on to the next generation. system likely to alter its qualitative and quantitative
protein composition in response to changing condi-
tions (environmental factors, temperature, gene
Genomics expression, administration of active substances,
Genomics is the term used for research on the form, etc.). For example, a caterpillar and the butterfly
function and interaction of genes in an organism. it changes into have the same genome. The reason
they look so different is that they have different
proteomes.
9
 Personalised Healthcare gets down 3 billion CHF
>2.5 years

to the molecular roots of disease

What makes individuals so similar and at the same time so unique? And what exactly
goes on in the body when people are healthy or sick?

1 million CHF

60 days

These questions have always intrigued scientists, but Molecular diagnosis, targeted therapy: cancer as gical factors can contribute to the development of
it took molecular biology to come up with the really a case in point cancer. All these carcinogens function in the same
important answers. Major milestones were the discovery way: they damage the life molecule DNA.
of the double helix (the structure of the life molecule One important insight derived from molecular research <CHF 10,000
DNA) in the early 1950s and the sequencing of the is that cancer is not just cancer. The term covers some Many such defects or damage will never impair the
Days <CHF 1,000
human genome at the beginning of the new millennium. 250 different conditions, almost all of which affect body functioning of our genetic systems, not least because Hours
tissues. While these conditions display major differences the cell has repair services at its disposal that can
Today, findings from new branches of research like in their symptoms and delayed effects, there is one quickly remedy irregularities like a DNA letter in the 2003 2008 Today In future
Human Genome James Watsons
genomics or proteomics enable researchers to refine thing that breast, lung, intestinal or skin cancer all have wrong place. But if there are alterations to genes
Project Genome
their understanding of diseases at the molecular level. in common: they are ultimately genetic diseases. that are particularly vital for the life of the cell, if the
This is the basis for innovative strategies combining defects cannot be repaired or compensated for, or if Cost and time involved in gene-sequencing
new diagnostic procedures and ongoing biotechnolog Some genetic defects triggering cancer are inherited, a large number of genetic defects accumulate in the
ical progress to fight diseases more effectively than others are acquired in the course of our lives as a result course of time, then cancer may be the result.
ever before. of factors that encourage cancer like tobacco smoke,
radiation or viruses. Additionally, life-style and psycholo- Such lasting changes interfere with important cellular If we want to beat cancer, we first have to understand
mechanisms that normally regulate and control how the genetics behind it, said American cancer researcher
cells proliferate. Cellular growth goes awry and uncon and Nobel Prize laureate Renato Dulbecco back in
trolled cell division is the upshot. The rogue cells oust the mid-1980s. Later, he added: Any change in the
Growth factor receptor signaling The heartland of cancer and damage healthy tissue. Things become even more functioning of one gene can therefore be accompanied
serious when these degenerate cells find their way by changes in the workings of multiple genes and
RTK into the circulation or the lymph system and ultimately proteins involved in the cells self-maintenance and the
establish themselves elsewhere in the body as second occurrence of disease. The new insights molecular
Common cancer mutations ary tumours, also known as metastases. biology had to offer on the genesis of cancer prompted
PIP2 PIP3
Dulbecco to call for the complete decipherment
(sequencing) of the human genome. A rough, incom-
PTEN Molecular science for better, more efficient plete version came out in 2001. Only two years later
healthcare the sequencing was complete and the full version was
Ras p110a p85
published.
PI3K TSC1
Thanks to ultramodern methods for sequencing the
Raf AKT TSC2 genome, including a series of innovative systems from The list of genes involved in cancer is by no means
Roche, todays scientists know of some 350 genes complete. This is why present-day scientists participat-
MEK involved in the genesis of cancer. Examples are the ing in the global Cancer Genome Project are looking
breast cancer genes BRCA1 and BRCA2. A more recent for other key mutations that cause and promote cancer.
example is a gene that has been found in a mutated The aim of this integrated international research venture
ERK Cyclin D1 Forkhead Bad mTOR
form in about 50 percent of all cases of skin cancer and is to detect all the mutations that cause the 50 most
Cell cycle Protein synthesis in approximately eight percent of all solid tumours. frequent kinds of cancer in humans.
p27 FasL Bcl-2
progression and and growth
proliferation
Survival

10 Roche Personalised Healthcare 11

 Molecular sciences provide new insights into

Once the molecular causes of a disease have been
identified, we have a chance of developing targeted
diagnostic methods and medicines adapted to the
genetic constitution of these degenerate cells. Perhaps
in future, physicians will no longer speak of skin or
lung cancer. Instead the focus will be on the respective
molecular blueprint and tumours with specific muta-
tions that can be diagnosed with gene-based methods
and treated with specifically targeted medicines, regard-
less of the part of the body that has been affected.
Personalised Healthcare is the strategy of the
future for cancer but for other diseases as well
1,000
Gene disease pathways. This improved understanding
What is a gene?
of disease mechanisms allows the development
Number of plausible targets
In its simplest form, a gene is a section of DNA of targeted treatments, resulting in efficiency
(deoxyribonucleic acid) bearing instructions increases in healthcare.
for a particular function. The instructions of the
best-known genes are carried out by mobile Disease
messenger molecules (messenger RNA, ribonu- mechanisms
cleic acid) transcribing the relevant section of the
DNA. Subsequently, the information is translated Pathways
into protein language by molecular production
sites (the ribosomes of the cell plasma) to produce
a specific protein molecule.

Personalised Healthcare is the strategy for the future, How many genes are there? Basic biological
not only in the case of cancer but also in fighting infec- Today, we know that human DNA contains more mechanisms
tious diseases like hepatitis C or the immune deficiency than 25,000 protein-coding genes. We also know
syndrome AIDS, metabolic disorders like osteoporosis, that defects in DNA lead to defects in RNA. This, Human
genome
or inammatory diseases like rheumatoid arthritis. in its turn, may produce proteins with defective Genetic
code
Indeed this strategy is already optimising the targeted structures, i.e. proteins that cannot perform
DNA structure
therapy for combating HIV that triggers AIDS. In osteo- the tasks they are supposed to perform in the
porosis it helps monitor therapy success, and in the organism. Observational
treatment of hepatitis C infections, it makes it possible biology
to say beforehand how long the medication will need What do genes have to do with disease?
to be administered in order to achieve lasting virological A chain of defects at the molecular level from
response in 80 to 90 percent of patients with HCV gene to protein can cause diseases. Modern
genotype 2 or 3. molecular biologists are convinced that there is Cells /organisms
no disease in which defective genes and their
subsequent signaling pathways are not involved
in some way.

10
Pre -1950s 1950/60s 1970/80s 1990/00s Today

12 Roche Personalised Healthcare 13

 Stomach cancer
What is stomach cancer?
Stomach cancer can develop in the tissue of the stomach
itself or in the junction between the oesophagus and the
stomach. In its early stages, the cancer is restricted to these
regions. If the disease spreads to the rest of the body in
the form of metastases (secondary tumours), it is referred
to as advanced or metastatic stomach cancer.
How common is stomach cancer?
Stomach cancer is the fourth most common kind of cancer
worldwide and the second cause of all cancer deaths.
It is diagnosed in about one million persons every year.
The disease is more widespread in Asia than in the West,
men are more frequently affected than women.
How is stomach cancer diagnosed?
Two main methods are endoscopy, in which a thin tube is
introduced into the stomach via the oesophagus, and radio-
logical examination. More recently, tissue diagnostics has
become one of the most important procedures of this kind.
Modern molecular diagnosis is able to detect the HER2
receptor. In about one of six stomach cancer patients, excess
amounts of this protein form on the surface of the tumour
cells and encourage their proliferation. Patients with a
high expression of HER2 receptors can be given targeted
treatment with monoclonal antibodies.
14
How is stomach cancer normally treated?
Stomach cancer is the Previously, stomach cancer was treated with a multimodality
fourth most common kind approach including surgery, combinations of chemotherapy
of cancer worldwide compounds and radiotherapy. Surgery can be successful
in the early stages of the disease. In the later stages,
chemotherapy treatment with medicines that inhibit cell
division and/or radiotherapy are usually the only options left.
Where Personalised Healthcare comes in
In January 2010, approval was given for a medicine devel-
oped by Roche to provide targeted treatment for advanced
stomach cancer patients with tumours on which the overpro-
duction of the HER2 receptor has been identified. The active
substance in this medicine is a biotechnological product.
In treatment it is combined with standard chemotherapy.
New therapeutic options
Approval was based on the findings of an international study
indicating that this new therapy option can clearly prolong
available for patients with
the lives of stomach cancer patients. overexpression of the HER2
receptor
The picture (top of page) shows stomach cancer tissue in a staining which is routinely used by pathologists
in the laboratory for the diagnosis of cancer.
The pictures on pages 17, 19 and 21 depict tissues from breast, lung and skin cancer.
Roche Personalised Healthcare 15
 Breast cancer
How common is breast cancer?
Every year, about 1.4 million new cases of breast cancer are
diagnosed worldwide. Advances in the treatment of breast
cancer are continuously being made but 450,000 women still
die of this disease each year.
How is HER2-positive breast cancer diagnosed?
On average, one in five breast cancer tumours displays an
overproduction of HER2 receptors on the tumour cells.
Targeted treatment homes in on these receptors. At Roche,
experts from both divisions work closely together to ensure
the high quality of HER2 tissue tests and to reliably identify
those patients who will benefit from targeted treatment.
This makes our tissue tests a crucial quality-assurance
component in the treatment of breast cancer worldwide.
Where Personalised Healthcare comes in
Patients with an overexpression of HER2 receptors can be
given targeted treatment with monoclonal antibodies pro-
duced by genetic engineering. Treatment decisions are
based on the precise determination of HER2 status. Since
it was first approved (1998 in the USA, 2000 in the EU),
targeted treatment of this kind has been administered to
almost one million patients diagnosed for HER2-positive
breast cancer. Response rates, general survival figures and
life quality for these patients have improved.
16
Under development
450,000 women die of At Roche, an antibody drug conjugate (ADC) is being studied
breast cancer every year for HER2-positive metastatic breast cancer. It is designed to
inhibit HER2 signaling and deliver a chemotherapy agent
directly into HER2-positive cancer cells. The antibody binds
to the HER2-positive cancer cells and is thought, based on
the data available, to block out-of-control signals that make
the cancer grow, while calling on the bodys immune system
to attack the cancer cells. Once the ADC is absorbed into
the cancer cells, it is designed to destroy them by releasing
the chemotherapy agent. The ADC attaches the antibody
to the chemotherapy agent using a stable linker which is
designed to keep the conjugate intact until it reaches specific
cancer cells (see illustrations).
Further, a new monoclonal antibody, a HER2 dimerisation
inhibitor, is being studied in early-stage and metastatic
HER2-positive breast cancer. HER receptor dimerisation
(pairing) is believed to play an important role in the growth
and formation of several different cancer types. The new
compound is the first investigational medicine developed to
specifically prevent the HER2 receptor from pairing with
other HER receptors. In doing so, it is thought to block cell
signaling, which may inhibit cancer cell growth or lead to the
death of the cancer cell. The mechanisms of action of this
and an already approved targeted medicine are believed to Almost one million patients
complement each other as both bind to the HER2 receptor
diagnosed for HER2-positive
but on different regions.
breast cancer received
targeted treatment
Roche Personalised Healthcare 17
 Non-small cell
lung cancer
How common is non-small cell lung cancer and what
molecular features does it display?
Non-small cell lung cancer is the most common tumour-
conditioned killer worldwide. Despite its apparently uniform
classification, this type of tumour varies with the genetic
defects underlying it. One example is a mutation of the
gene responsible for the formation of the epidermal growth
factor receptor. The mutation is found in approximately
30 percent of all patients from Asia, and in about ten percent
of those from western countries.
In another subgroup of patients suffering from this disease,
the surfaces of the tumour cells display an above-average
number of different receptors. Like the epidermal growth
factor receptor, these receptors induce out-of-control prolif-
eration of the tumour cells.
Four stages of lung cancer
From locally restricted lesions to advanced
metastases of all types (left to right)
18
Where Personalised Healthcare comes in
Most common Up to now, surgery and chemotherapy have been important
Targeted treatment
tumour-conditioned treatment options. Today, however, patients suffering from blocks the cancer cells
killer worldwide non-small cell lung cancer and having the specific mutations receptors and thus
mentioned above first, can be identified by a molecular test. inhibits its growth
A medicine developed by Roche can block these receptors and
disrupt the signal transmission pathway to the inside of the cell,
thus blocking tumour growth and triggering tumour cell death.
A study published in June 2011 indicates that if patients with
advanced non-small cell lung cancer displaying this mutation
are treated with this medicine as first-line therapy, it nearly
doubled the time people lived without their disease getting
worse compared with standard chemotherapy. In August 2011
the EU authorities approved use of this medicine in treating
this aggressive form of lung cancer in first-line therapy. This
medicine has already been approved for the later-line treatment
of advanced or metastatic non-small cell lung cancer.
A tissue test now in the course of development can also
detect the receptors for the different subgroup that can cause
uncontrolled proliferation of lung cancer cells. A novel drug
candidate currently being developed by Roche binds specifically
to these receptors. In conjunction with another active sub-
stance, it can prolong survival without further deterioration of
the patients condition. This is the provisional outcome of a
clinical study published in June 2011.
Roche Personalised Healthcare 19
 Skin cancer
What is metastatic melanoma?
Metastatic melanoma is the deadliest and most aggressive
form of skin cancer. A metastatic melanoma develops when the
melanocytes the pigment cells in the skin proliferate in
an uncontrolled way. If identified and treated early, melanomas
respond well to treatment. But once metastases (secondary
tumours) have formed and spread through the body, the
chances of recovery are slight.
How common is metastatic melanoma and
what causes it?
Every year, some 200,000 new cases are diagnosed world-
wide, most of them in Europe, North America, Australia and
New Zealand. The ultraviolet rays of the sun are probably the
most significant causative risk factor. Fair-skinned and red-
headed people are more likely to be affected by melanoma.
Individuals with many or large pigmented moles and people
from melanoma-prone families are also more likely to develop
the disease.
How is metastatic melanoma diagnosed and treated?
Any change in the size, form, colour or sensitivity of an
existing pigmented mole or the formation of a new one can
be an indication of melanoma and should be looked at by
a doctor. Metastatic melanoma can be treated by surgery,
radiation/chemotherapy or therapies fortifying the immune
system. The therapies are either combined or used individu-
ally depending on the stage the disease has reached.
20
Where Personalised Healthcare comes in
Metastatic melanoma Skin cancer therapy is the latest example of the approach
is the most aggressive successfully combining accurate molecular diagnosis with
kind of skin cancer targeted therapy. A new active substance developed jointly
by Roche and Plexxikon, a member of the Daiichi Sankyo
Group, attacks the protein product of the altered (mutated)
gene. The mutated gene causes uncontrolled division of
the skin cells. Roche has also developed a companion test
to go with the new medication.
Scientists first discovered the mutated gene in metastatic
melanoma cells back in 2002. In the meantime it has been
detected in approximately half of all these patients. Given this
new molecular-biological information, the active substance
took only a relatively short time to develop. Targeted therapy
is accompanied by a test designed to detect the mutation
in the tumour at a molecular level. The test thus identifies
patients who are likely to respond to the new substance.
The outcome of a clinical study published in June 2011 shows
that the new active substance can prolong the survival of
patients suffering from a metastatic melanoma with the muta-
tion described above. Subsequently the active substance First approval simulta-
agent was given priority review status by the US drug approval neously of the diagnostic
authority FDA. In May 2011 applications were submitted both test to confirm the mutation
in the USA and in the EU for approval of the active substance and the new medicine which
and the companion test. In the US, the health authorities
attacks the protein product
simultaneously approved both the diagnostic test and the
medicine, in August 2011. of the mutated gene
Roche Personalised Healthcare 21
 Hepatitis B and C
infections
How common are hepatitis B infections?
Up to two billion people worldwide have become infected with
the hepatitis B virus (HBV). In many cases the immune system
can deal with the virus, but about 350 million of these people
develop a chronic infection that can ultimately lead to cirrhosis
of the liver and cancer of the liver cells. Estimates suggest
that some 600,000 people are killed by the consequences of
a chronic hepatitis B infection every year.
The Personalised Healthcare approach to
hepatitis B therapy
The number of viruses and the specific antigens of the virus
influence the clinical course of the infection and patient
response to therapy. The various subgroups of the hepatitis B
virus can be identified with new molecular diagnostic methods
developed by Roche. The results of these tests assist doctors
in predicting the outcome of a standard therapy slowing down
the proliferation of the hepatitis B virus and stimulating the
bodys defence system.
Evidence of a declining concentration of viral protein indicates
the probability of therapy success. Based on this marker,
Roche is currently investigating various treatment strategies
that will allow a more personalised approach to chronic
hepatitis B infection therapy in the future. Due to the immune
stimulation effect of this targeted treatment, the number of
patients remaining free of the disease years after therapy ends
is steadily increasing.
22
How common are hepatitis C infections?
350 million people Hepatitis C viruses (HCV) also cause acute and chronic liver 200 million people
are chronically infected disorders that can result in liver failure, cirrhosis and cancer are chronically infected
with HBV of the liver. About 200 million people worldwide are infected with HCV
with hepatitis C viruses.
The Personalised Healthcare approach to
hepatitis C therapy
Today, we know that there are four subtypes of the hepatitis
C virus. They differ not only in their molecular structure but
also in the extent to which they respond to treatment. The
various types can be identified by molecular tests developed
by Roche enabling predictions of how long the treatment
will take and how likely it is to succeed.
Additionally, in the last few years a single mutation in
patients genome has been found to correlate to treatment
outcomes (single nucleotide polymorphisms, SNPs).
At present, Roche is working on new active substances
designed to help fight the hepatitis C virus. Different treat-
ment regimens will be tested according to the patients
genome status which will allow a personalised treatment
once development is completed.
Roche Personalised Healthcare 23
 Osteoporosis
What is osteoporosis and how common is it?
Osteoporosis is a disease in which the density and quality
of bones are reduced. Women are affected four to five times
as often as men. Statistically, one in three bone fractures in
postmenopausal women is caused by osteoporosis, with the
likelihood of fractures increasing in old age.
Challenges of osteoporosis treatment
Treatment of osteoporosis with bisphosphonates requires
a degree of therapy compliance from the patient. This is
especially difficult since osteoporosis is largely an asymptom-
atic disease, meaning that patients are not likely to feel
different if they take their medication or not.
An existing method for measuring bone density (DEXA scans)
can be used to determine whether treatment is having the
desired effect. However, due to the slow growth of bone,
it can take as long as one year before any indicator of the
success or failure of therapy can be evaluated by these scans.
Experience tells us that many patients lose the motivation to
take the medication. In fact studies * suggest that more than
50 percent of patients discontinue treatment in the first year.
24
One in three bone fractures
in postmenopausal women
is caused by osteoporosis
Fractures are the main cost driver
Osteoporosis becomes especially expensive when fractures
occur. Although fewer than 5% of those affected actually
suffer a fracture, fractures account for almost two-thirds of
total osteoporosis costs. The most frequent and most expen-
sive fracture is that of the hip. Each fracture that can be
prevented helps ease the burden on healthcare systems.
The costs of osteoporosis
In Germany alone, to give just one example, osteoporosis
affects about 6.3 million people over age 50 *. Thats roughly
one-fifth of the population in this age group. In the patient New tests developed by
group over age 74 as many as one in three patients are
Roche provide information
affected. Yet only one-third of osteoporosis sufferers receive
on the metabolic activity
specific therapy. One study * * calculated that osteoporosis
resulted in annual costs of more than five billion euros, thus of the bones
making it one of the expensive high-prevalence diseases
alongside diabetes or heart disease.
Where Personalised Healthcare comes in
New tests developed by Roche use bone markers, which are
identifiable from blood samples and contain information on
the metabolic activity of the bones. These tests can tell us
after only a few days whether treatment is having an effect.
* Best study, German Institute of Health Care and Social Research, 2011
* * Osteoporosis International, 2007, 18:7784
Roche Personalised Healthcare 25
 Personalised Healthcare
the benefits as seen by the patient and the experts

Patient
Doretha Dee Burrell
Physician
Insurance executive
Dr Caroline Robert
Prof. Thomas Szucs

Researcher
Dr Shirin Khambata Ford

Medical laboratory scientist

Dr Jos Gilberto Vieira

Investigator
Prof. Henry Lik-Yuen Chan

26 Roche Personalised Healthcare 27

 The immediate combination of diagnosis,
therapy and monitoring of treatment success
in hepatitis B infection is a major step forward.
This increases the benefits for our patients
enormously!

About 350 million people are infected with the hepatitis B virus;
about 75 percent of these people are living in Asia. By predicting
better and earlier who is going to respond to therapy allows us
to provide more effective care. Assurance of our patients also
increases their compliance to therapy, resulting in an increase of
the desired treatment outcome. For patients who do not respond
very well we may be able to modify treatment to increase their
chances to respond and benefit from modern therapies.

Director, Cheng Suen Man Shook Centre

Investigator for Hepatitis Research; Director, Centre for
Liver Health, The Chinese University of Hong Kong,
Prof. Henry Lik-Yuen Chan
Hong Kong, China

28 Roche Personalised Healthcare 29

 Its a very exciting time for us. We are all
aware that we are entering a new era of skin
cancer treatment!

Skin cancer was an area of high unmet medical need, but

with the new compounds becoming available we are going
to improve the survival of our patients. The stratification and
targeted treatment of this fatal disease represent a major
step forward. As next steps we have to establish screening
for the relevant genetic mutations. We also need to learn
how best to combine the various compounds, some still in
development, in order to maximise impact and benefit for
patients.

Physician Chef de Service

Cancer Institute Gustave Roussy
Dr Caroline Robert Villejuif near Paris, France

30 Roche Personalised Healthcare 31

 The option of targeted treatment
gave me hope and a better quality of life!

Hearing the words, you have breast cancer were the most
devastating words I had ever heard. I was so frightened, not
sure how life would be for me going forward. It gives me
peace to know that my oncologist believed in targeted therapy
and I am most grateful to have been administered such a
treatment which has improved the quality of my life for the
past four years.

Patient
Philadelphia, USA
Doretha Dee Burrell

32 Roche Personalised Healthcare 33

 In my view, Personalised Healthcare will
be the only way of husbanding our resources
in a way that makes good business sense!

For the insurance companies, Personalised Healthcare

is extremely important because in future we will simply
not be able to afford to stick to the one-size-fits-all
method of providing patients with medicines or technologies
in a rough-and-ready manner. Professional analyses tell
us that both from an economic and from a medical view-
point, diagnostics-based, optimised therapy, say for
hepatitis C, is superior to standard treatment strategies.

Insurance executive Chairman, Helsana Insurance Group

Prof. Thomas Szucs Zurich, Switzerland

34 Roche Personalised Healthcare 35

 As a researcher strongly committed to driving
Personalised Healthcare forward, I appreciate
some of the distinct advantages of having both
Pharmaceuticals and Diagnostics under one
roof .

In the field of oncology it is particularly helpful to involve

diagnostics as early as possible in clinical development.
This increases the efficiency and speed of discovering and
developing patient selection markers that could have an actual
impact in the clinic, and make an important difference to
patients lives. In order to do this at a high frequency for
our drug candidates across multiple indications, a dedicated
in-house diagnostics effort is required, and Roche clearly
has one of the largest and strongest in the industry.

Scientific/Biomarker expert Senior Biomarker & Experimental Medicine Leader

Oncology Translational Medicine
Dr Shirin Khambata Ford Roche Nutley, USA

36 Roche Personalised Healthcare 37

 We see tremendous changes in our tasks.
With Personalised Healthcare, diagnostic
services gain relevance rapidly since our
test results become integral factors for the
development of modern treatment strategies.

Increasingly, treatment decisions are based on sophisticated

laboratory analysis covering complex diseases, cancer for
example. Modern diagnostic methods enable us to provide
precise data and thus offer a reliable basis for treatment
decisions. Rapid initiation of the right therapy and an
optimised use of the limited resources of our healthcare
system result from this strategy. This is a real win-win
situation for patients and for society as a whole.

Medical laboratory scientist Medical Advisor, Fleury Laboratory

Dr Jos Gilberto Vieira So Paulo, Brazil

38 Roche Personalised Healthcare 39

 Research and development at Roche:
a unique symbiosis
There is unrestricted, cross-divisional cooperation between scientists in research
and development at Roche from early research all the way through to the
marketing of our products. This is a unique asset that distinguishes Roche from
other companies. Close cooperation of this kind is also the basis for the successful
implementation of our Personalised Healthcare strategy.

The diagnosis and therapy options for skin cancer 22

(see pp. 2021) submitted to the drug authorities for Number of
approval are an instance of the advantages of having companion
test projects
research and development under one roof. The entire
process from initial clinical studies to the application for
approval took only five years. Normally, seven to eight
years are standard. For patients waiting for a treatment
option, this time gain makes a very important difference. 147

As the syndromes referred to in this brochure indicate,

a number of our products have been successfully
integrated into personalised therapy strategies in the
fields of oncology, virology and metabolic disorders.
Various other targeted medicines and companion tests 7
are at an advanced stage of development, including
active substances against breast and lung cancer,
hepatitis C and asthma. At present, Roches research
efforts are focused very strongly on the development of 94
new therapies for inflammatory diseases and disorders
of the central nervous system.
3

Positive data from a large number of development

projects have recently been presented at major scientific 66
and medical conferences and published in renowned
journals. This is another impressive indication that
2
Roches Personalised Healthcare strategy is a front-line
campaigner against diseases and rapidly gaining
significance for the benefit of patients. 1
36

24

2006 2007 2008 2009 2010 2011

Increase in collaborations between Roche

Pharmaceuticals and Roche Diagnostics

40
F. Hoffmann-La Roche Ltd
Group Communications
4070 Basel, Switzerland

October 2011

www.roche.com

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